Process for preparing derivatives of 7-amino-desacetoxy cephalosporanic acid

Abstract

Process for preparing cephalexine monohydrate and cephadroxyl monohydrate, according to which a reaction is carried out of a mixed anhydride prepared from a Dane salt of phenylglycine or p-hydroxyphenyl-glycine with a chloroformiate, with an aqueous solution of 7-ADCA in a solvent selected from the group comprising dimethyl sulphoxide, dimethylacetamide, formamide, dimethylformamide and dioxane.

What we claim is: 
     
       1. A process for preparing derivatives of 7-amino-desacetoxy cephalosporanic acid having the formula ##STR4## wherein R is --H or --OH, wherein a mixed anhydride having the formula ##STR5## wherein R is --H or --OH, R 1  is methyl, ethyl or isobutyl, and R 2  is methoxyl or ethoxyl, is added at a temperature in the range of -60° C. to -10° C. to a solution obtained by dissolving 7-ADCA with excess triethylamine, in an amount in the range of 1.05-1.25 moles over 7-ADCA, in a solvent selected from the group consisting of dimethyl sulphoxide, dimethylacetamide, formamide, dimethylformamide and dioxane, in the presence of water and at a temperature ranging between 0° C. and +20° C., the mixed anhydride being in an amount at least equimolar with respect to the amount of 7-ADCA, then removing the enamine group by lowering the pH of the reaction mixture to 0.8-2.5 by adding an aqueous solution of an inorganic acid, and finally isolating said derivative product. 
     
     
       2. A process according to claim 1, wherein the solvents of 7-ADCA are in an amount ranging between about 10 and 25 moles per mole of 7-ADCA.